Production of 131-I iodide capsules in Argentina

(1) (1)
, G. Casale(1), L. Silva(1), M. Nicolini(1), P. Apolinario(1), G.
J.O. Nicolini , G. Baró
Oviedo , G. Orlandino , R. Caro(1), M.J. Salgueiro(2), N. Leonardi(1), M. Zubillaga(2)
(1) (1)

and P. Zubata(1)
(1)
Laboratorios Bacon S.A.I.C., Uruguay 136, Villa Martelli, Buenos Aires, Argentina
(2)
Cátedra de Física, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires,
Junín 956, Buenos Aires, Argentina

Abstract

It is well known that 131I iodide capsules are better suited to be taken by the patient than the
corresponding solution. Therefore most Pharmacopeias have monographs for 131I in both pharmaceutical forms:
solution or capsules, for diagnosis but principally for therapeutic purposes. In Argentina this radiopharmaceutical
has been made commercially available in November 2007. At this time Bacon Laboratories SAIC started its
production, authorized by the Health and Nuclear Regulatory Authorities.
131
I, in the pharmaceutical form of capsules, have evident advantages in radioprotection for the patients
and the personnel involved in its administration. The intake of a 131I provokes frequently that the external part of
the mouth (principally if there is a beard and/or a moustache) undergoes an external contamination. This problem
is enhanced if the patient has some motor difficulties to take the glass with the solution. In this case he will need
assistance from the medical or technical staff, who will receive a much greater radiation dose than in normal
cases.

In the capsule of 131I iodide, the solution is adsorbed on a sodium phosphate matrix. The capsule is in a
plastic tube contained in an appropriate lead shielding. To take the capsule, the patient inclines the open lead
shielding containing the capsule in the direction of the mouth. Once the capsule is in the mouth it is swallowed
with a little portion of water. After its intake, the radiopharmaceutical is absorbed from the gastrointestinal tract.
If a patient is unable to carry out the intake, the assistance by medical or technical staff is easy with practically
no radiation harm, since the 131I is shielded by an adequate lead thickness. It is evident that the hands and
external face of the patient are also protected since no possibility of contamination exists.

The aim of this work is to present the production procedure, the packaging of the capsules and the
decrease of the dose received by the involved personnel. All the radionuclide, radiochemical and pharmaceutical
quality control procedures required by the U.S. Pharmacopeia are carried out at the laboratory.

KEYWORDS: 131-I capsules; radioprotection improvement; intake advantages.

INTRODUCTION

The oral administration of 131I iodide for diagnostic or therapeutic purposes has been one of
the first nuclear medicine procedures.

Even though the procedure is safe, it has been frequently observed that there are certain risks
of contamination of the face of the patient or the medical personnel involved in the administration or
even of the nuclear medicine center if the radioisotope is taken as a solution. This may occur
principally if the patient has motor disorders. Therefore, since many years, it has been recommended
to administrate the radioisotope in capsules, especially for therapeutic purposes. This procedure
precludes almost completely the external contamination of the patient and the medical personnel
involved in the administration. At the same time, the irradiation of the medical personnel is also
strongly decreased.

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 In order to produce this radiopharmaceutical it is necessary to have a 131I with a high activity
concentration. Owing to the fact that since some years ago Argentina is producing 131I from fission
products rather than by n,γ reaction on Tellurium, our laboratory decided to implement the techniques
for the production and analysis of 131I capsules.
MATERIALS:

Gelatin capsules are prefilled in a clean area with an inert mixture of anhydrous Di-Sodium Phosphate
with traces of Sodium Thiosulfate and EDTA. All drugs are purchased from BAKER. A PC
programmable pump with a disposable syringe is used to dispense the calibrated activity into the
prefilled capsules. 131I carrier free without reduction agents is supplied by the Argentine National
Atomic Energy Commission (C.N.E.A.) with an activity concentration higher than 18,5 GBq/ml.
The hot cell is designed in order to manipulate high activities of 131I with a special filter system in
order to provide a clean and shielded cell. The system was approved by the Nuclear Regulatory
Authority (A.R.N.).
The capsule shielding was designed by BACON LABS in order to minimize the dose absorbed by the
patient as well as by the involved medical personnel. The shielding is dose/weight optimized. The
capsule is taken directly from the shielding by the patient and swallowed.
The shielding can transport up to 7,4 GBq with a weight of 1300g and has a sealed flask that opens
together with the shielding top.

PRODUCTION METHOD:

The procedure is semiautomatic. First of all, the pre-filled capsules and the raw materials are placed
into the hot cell, and afterwards the 131I is positioned inside. The syringe is filled with the radioiodine
solution and the information of the activity to be dispensed is entered into a PC program, together with
the calibration date and batch information. The program calculates and dispenses the required volume
in each capsule automatically, but there is a restriction of the volume due to the limited phosphate
capacity to absorb liquids. Therefore, the capsule accepts a limited volume and consequently the
activity is limited depending on the concentration of activity of the 131I solution.
After dispensing, the capsule is closed by means of a remote manipulator and sent outside the hot cell
by a duct, directly into the shielding.

Figure 1: Production Scheme

CALIBRATION PROCEDURE:

The ionization chamber VEXCAL (Vexsa, Buenos Aires, Argentina) has a shaft sufficiently large to
enter the shielding with the capsule. A statistic procedure was carried out in order to calibrate the
activity measurement of the capsule with the shielding. For this purpose 30 capsules were measured

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with and without shielding in order to obtain a calibration factor from the ratio of the activities without
and with the shielding. This ratio had a standard deviation not higher than 3 per cent. Eventually the
system is tested with a capsule with and without shielding during each production, verifying thereby
the mentioned factor. The system demonstrates to be sufficiently strong for the calibration of the
capsules.

QUALITY CONTROL:

The iodine 131I capsules quality control was performed according to the corresponding US
Pharmacopeia monograph (1).

DOSIMETRIC STUDY:

In the present study we only consider the external dose absorbed by a technician who manipulates 131I
capsules or oral solution in order to administrate therapeutic activities of 131I to a patient in a nuclear
medicine center. We estimate distances, time and shielding for each operation for comparative
purposes. The doses are obtained by mean of calculations using a MicroShield V5.03 program (2).

Case 1:

It is a solution of 50 mL of water with an activity of 131I for an oral administration of 3,7 GBq.
The table 1 summarizes all the technical procedures with the doses involved.

Table 1

hand body D* D*
time shield dist. dist. Hand Body Hand Dose Body Dose
PROCEDURE (sec) (cm) (cm) (cm) (mSv/h) (mSv/h) **(mSv) **(mSv)
1- Hang up the
shield 10 2 1 40 1,580 0,012 4,39E-03 3,33E-05
2- Activity
measurement 30 0,5 15 40 7,950 0,920 6,63E-02 5,52E-04
3- Uptake of activity
with the syringe 30 5 40 10,500 0,940 8,75E-02 7,29E-04
4- Activity
measurement 30 0,5 15 40 7,950 0,920 6,63E-02 5,52E-04
5- Activity dilution
in a glass of water 15 5 40 10,500 0,940 4,38E-02 1,82E-04
6- Administration of
the glass to the
patient 15 5 40 12,500 0,940 5,21E-02 2,17E-04

TOTAL DOSE **(mSv) 3,20E-01 2,27E-03

Case 2:

It is a capsule with an activity of 131I for an oral administration of 3,7 GBq.

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The table 2 summarizes all the technical procedures with the doses involved.

Table 2
hand body D* D* Hand
time shield dist. dist. Hand Body Dose Body Dose
PROCEDURE (sec) (cm) (cm) (cm) (mSv/h) (mSv/h) **(mSv) **(mSv)
1- Hang up the
shield 10 1,9 2 40 7,47 0,0329 2,08E-02 5,76E-05
2- Activity NOT
measurement NECESSARY
3- Take the activity NOT
with the syringe NECESSARY
4- Activity NOT
measurement NECESSARY
5- Put the activity in NOT
a glass of water NECESSARY
6- Give the glass to NOT
the patient NECESSARY
7-
Adminsitration
of the capsule
to the patient. 5 2 40 7,47 0,0329 1,04E-02 1,44E-05
TOTAL DOSE** (mSv) 3,11E-02 7,20E-05
D*:Dose Rate: Deep Dose Equivalent Rate, ICRP 51-1987
** : Rotational geometry

Discussion:
In both cases the doses involved are relatively low, but if we consider that in Argentina there is a
radioiodine (131I) consumption between 370 GBq and 555 GBq (10 Ci-15 Ci) per week, we can
calculate (considering 370 GBq/week and 50 weeks per year) that the Collective Dose (3) for this
therapeutic practice is:
Case 1 (131I solution): 11,35 mSv.man
Case 2 (131I capsules): 0,36 mSv.man
It should be pointed out that we are only taking into account the external dose, but for a real evaluation
of the advantages of the use of capsules, the risk of contamination of the patient and/or the medical
personnel should also estimated. Unfortunately we had not enough data for a rough quantitative
estimation of this difference, but intuitively it cannot be overseen that the probability of a
contamination is much higher in the case of the use of the solution, with which the control of the risk
of a contamination is very difficult. Obviously the risk of contamination due to the use of capsules is
negligible.

Conclusions:

The use of 131I capsules for therapeutic administration in the medical practice has advantages which
should expand its use for the benefit of the patient and the exposed personnel. It should also be taken
into account that the use of 131I capsules is a worldwide practice and the advantage of its local
production should convince nuclear medicine physicians to use them with confidence.

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Bibliography:

1- Unites States Pharmacopeia 29 NF 24, Monografías oficiales, yoduro de sodio I-131, cápsulas
(spanish version). (2005). 2483-2484.
2- Microshield: http://www.philrutherford.com/radiation_software.html.
3- ICRP 60. Recomendaciones 1990. Comisión Internacional de Protección Radiológica.
Sociedad Española de Protección Radiológica.